1. Field of the Invention
This invention relates to dermatologically acceptable film-forming emulsions containing iodine. More specifically, it relates to film-forming emulsions useful in promoting asepsis on skin. Methods of using the emulsions are also within the scope of the invention.
2. Description of the Background Art
In order to reduce the risk of infection in patients, it has become standard practice to topically apply an antimicrobial agent to compromised areas such as surgical incision sites, wounds, burned areas, catheterization sites and injection sites. Topical application of antimicrobials has been utilized to reduce the bacteria count on skin in the area of application.
Topical application of antimicrobial agents has been accomplished using, for example, solutions, tissues, lotions, and ointments. Because microorganisms may survive the initial application of the antimicrobial agent, it is often necessary to reapply the agent in order to provide continued asepsis. Also, because antimicrobial agents are often water soluble, and therefore, subject to removal from the application site by water or bodily fluids, reapplication of the antimicrobial agent may be necessary to assure continued bactericidal activity. In particular, polyvinylpyrrolidone, which is widely utilized as a carrier for the broad spectrum antimicrobial iodine, is water soluble and is rapidly washed away from skin by irrigation or bodily fluids.
Increasing the water and bodily fluid resistance of topically applied antimicrobial agents and thereby increasing the substantivity and length of bactericidal activity has been a long standing goal in the art. In particular, there are several examples of inventions with the aim of improving the substantivity of the N-vinylpyrrolidone/iodine complex. Compositions that are able to form a water insoluble film can, in addition to providing long lasting antimicrobial activity, also provide a protective layer for sensitive tissue such as is present in burn wounds.
Organic solvents such as ethyl alcohol or isopropyl alcohol are often used as the antimicrobial agent and/or as the solvent carrier for other antimicrobial agents. Alcohols and other organic solvents can be irritating to skin tissue and are not suitable for use on sensitive tissues such as burn wound sites and mucosal tissue. Often the vapors of the organic solvents are toxic and/or flammable.
The addition of iodine to colloids or emulsions has in the past been found to be destabilizing to the system. For example, U.S. Pat. No. 4,364,929 to Sasmor et al. discloses an aqueous germicidal colloidal lubricating gel comprising iodine and a gel forming colloid. In the background discussion at column 2, lines 37-42, the corrosive and oxidizing nature of iodine is discussed, noting that it destroys the stability of most pharmaceutical compositions and, in particular, colloidal lubricating gels. The patentees disclose that when iodine is added to a carbohydrate polymer in the presence of a substrate capable of forming an iodophor, such as povidone, a stabilizing effect is observed which prevents the destruction of the colloidal properties of the carbohydrate polymer by iodine.
Polyvinylpyrrolidone containing polymers complexed with iodine have been utilized as film-forming compositions. These compositions require high amounts of vinylpyrrolidone with correspondingly high amounts of iodine to render the polymer insoluble in water. These films would be extremely dark, so that viewing through the film would be virtually impossible. Due to the relatively high iodine content of the prior art systems, applicants expect that these emulsions would have a relatively short shelf life.
European Pat. No. 107,277 discloses an antimicrobial film consisting of 30 to 80 wt. % vinyl acetate and 20 to 70 wt. % vinylpyrrolidone copolymer combined with iodine and/or bromine to provide 2 to 25% available halide in the final product. The copolymer may be prepared by solution, suspension, precipitation or emulsion polymerization and is complexed by contacting with a 10 to 50% solution of halogen in an alcohol solution. The complex product is diluted with water and azeotropically distilled to form a viscous liquid product. The product may be used in its viscous state as a coating or can be diluted with an inert solvent such as water or alcohol for use as a liquid or aerosol spray.
German Pat. No. 2,557,607 discloses the preparation of a water insoluble copolymer having vinylpyrrolidone as one of the constituent monomers. The copolymer is converted into an insoluble addition compound by using a sufficient amount of iodine regardless of the initial solubility of the starting polymer. The amount of iodine required for this purpose is usually above 60% by weight based on the weight of the polymer. If the starting polymer is water insoluble, the iodine content of the adduct is generally in the range of from 0.1 to 50% by weight, based on the weight of the polymer. The formation of a film from an emulsion of the iodophor polymer is disclosed at the paragraph bridging pages 13 and 14.
A disadvantage of emulsion system film-forming compositions long recognized in the art is that such systems are expected to require comparatively long dry times. British Pat. 1,465,190 describes polymer in water emulsions which ". . . dry, i.e., form films, rapidly when placed on the skin, normally within about 4 to 6 minutes." The dry time recited above that the British patentees considered to be rapid is now considered to be too long for practical application. Surgeons and nurses prefer that any film-forming presurgical prep be dry to the touch in 2.5 minutes or less, and preferably less than 2 minutes.
U.S. Pat. No. 2,804,073 to Gallienne et al. discloses a film-forming composition. This composition can be either a polymer in organic solvent solution or a polymer-in-water emulsion. Organic solvents are used when dry times on the order of 5 minutes are desired, while a water emulsion is used when it is desired to increase the dry time to about 15 minutes or more. The cohesive strength of these films is greater than their adhesive strength, thus enabling them to be peeled intact from the skin to which they are applied.
U.S. Pat. No. 3,244,658 to Grosser et al. discloses the preparation of a stable aqueous emulsion containing a polymeric N-vinyl lactam. This emulsion provided a film which apparently was a mixture of a water soluble N-vinyl lactam homopolymer and a benzene soluble acrylic ester homopolymer. The patentees found that copolymerization of a N-vinyl lactam monomer and acrylic ester monomer in about equal amounts yielded an unstable emulsion, even without addition of I.sub.2. As disclosed in column 3, lines 52-62, the polymer formed by the process of the patent is a graft copolymer of an acrylic ester on a polymeric N-vinyl lactam substrate. No disclosure additionally complexing iodine with this polymer is provided.
U.S. Pat. No. 4,271,149 to Winicov et al. discloses germicidal iodine compositions comprising an aqueous solution of elemental iodine and at least one organic substance which slowly reacts with iodine. Iodine loss during the extended storage of the composition is controlled by providing iodide ion and iodate ion in a controlled pH range so that lost elemental iodine is restored by the reaction of iodate and iodide in the presence of hydrogen ions.
U.S. Pat. No. 4,374,126 to Cardarelli et al. discloses a film-forming antimicrobial material which comprises an alcohol soluble carboxylated polyacrylate, an antimicrobial agent such as bacitracine or iodine, a difunctional amide as a crosslinking agent and an adhesion promoting material. As disclosed at column 4, lines 53-61, the film-forming material is prepared in an ethyl alcohol and water solution.
U.S. Pat. No. 4,542,012 to Dell discloses a film-forming polymer which is the reaction product of 1) a prepolymer having a plurality of isocyanate functionalities, 2) a polyvinylpyrrolidone polymer and 3) a chain extender for the prepolymer and the polyvinylpyrrolidone polymer. This film-forming polymer is complexed with an antimicrobial agent, specifically iodine. The film-forming composition is applied to the skin as a solution in a volatile solvent such as ethanol or isopropanol.
U.S. Pat. No. 4,584,192 to Dell et al. discloses a film-forming copolymer consisting of copolymerized A, B and C monomers wherein A is an acrylic acid ester having 2 to 14 carbon atoms or is a methacrylic acid ester of 7 to 18 carbon atoms, B is a methacrylic acid ester of 1 to 6 carbon atoms, and C is an N-vinyl lactam which is from 1 to 15% of the total weight of all monomers in the copolymer. This film-forming copolymer composition is complexed with iodine. The composition is applied to the skin from a fugitive solvent, such as ethanol, isopropanol and acetone. Application of these solutions of water immiscible polymers in solvent to wet surfaces can result in precipitation of the copolymer and poor film formation. Organic solvents are utilized due to the need to have a carrier for the water insoluble copolymer and in order to provide a quick formation of dry films through the use of rapidly drying, volatile solvents.
The prior art has not provided a film-forming composition which is totally acceptable from the standpoint of convenience, nonirritation, nonflammability even before drying and safety and efficacy in promoting asepsis on skin. A good film-forming composition should be dermatologically acceptable and capable of application conveniently in a water based mixture which dries quickly on skin. The film resulting from application of such an emulsion should be water and body fluid resistant and substantially tack free, and should permit facile transmission of water vapor therethrough. The film should be clear to permit, for example, viewing of the site where an incision will be made during a surgical procedure. It should further adhere suitably to skin and be capable of releasing an antimicrobial agent onto the skin over a period of time. The film should be soluble in a dermatologically acceptable solvent such as a lower alkyl alcohol which may be used as or in a remover solution which is employed to remove the film when desired.
The film-forming emulsion of the present invention successfully meets the aforementioned criteria.